POS0694 MOLECULAR PHENOTYPING OF GIANT CELL ARTERITIS PATIENTS: ANALYSIS OF THE SERUM PROTEIN PROFILE USING A HIGH THROUGHPUT METHOD
Authors: F. Zingg, A. Gloor, C. Polysopoulos, P. Villiger, B. Maurer, L. Christ
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> There is a lack of biomarkers to profile phenotypes in giant cell arteritis (GCA) and predict potential complications. Serum protein profiling may identify molecular-based phenotypes and facilitate personalized medicine approaches. <h3>Objectives</h3> To investigate the serum protein signature of clinically defined GCA phenotypes and to evaluate whether serum protein-based profiling identified distinct patient clusters. <h3>Methods</h3> We analyzed baseline serum samples from 16 patients with new-onset GCA enrolled in the GUSTO trial (NCT03745586) [1]. Serum samples were collected prior to treatment or with the lowest prior GC-exposure. In total, 1436 differentially expressed proteins (DEPs) were assessed based on proximity extension assay technology. T-test (threshold, adjusted p-value &lt;0.05) was performed with adjustment for multiple testing (Benjamini-Hochberg) to identify DEPs. Supervised and unsupervised cluster analyses were performed. Supervised analysis was stratified based on the three following clinical phenotypes: presence or absence of (i) cranial and (ii) polymyalgia rheumatica (PMR) symptoms, and (iii) response to treatment within the GUSTO trial. <h3>Results</h3> Differences in the serum protein profile were observed based on the presence of cranial GCA and treatment response within the GUSTO trial. We identified 18 DEPs for cranial vs. non-cranial GCA, covering proteins involved in endothelial function (ECE1) or Th17 signaling (IL17RA), and 24 DEPs for response vs. non-response. GCA patients with non-response displayed among others a pronounced Th1 (IL2, IL12) and altered BAFF/APRIL signature. We found no difference based on the presence or absence of PMR-symptoms. Unsupervised hierarchical cluster analysis of the serum protein profile revealed three distinct patient clusters (Figure 1). There was no separation between patients based on clinical parameters except for a tendency to separate GCA patients with (cluster 2) from patients without PMR-symptoms (cluster 1). <h3>Conclusion</h3> Upon further validation, in GCA, molecular profiling of patients based on serum protein signatures has great potential for future individualization of patient management. This is the first study to phenotype new-onset GCA based on the serum protein signature. GCA patients with cranial symptoms and treatment response display a distinct serum protein signature. We found a tendency to cluster GCA patients with concomitant PMR-symptoms. Our findings of different protein signatures might facilitate personalized treatment approaches in GCA. <h3>Reference</h3> [1]Christ, et al. Lancet Rheumatol, 2021 <h3>Acknowledgements</h3> We thank Sabine Hasler, Andrea Ziörjen Kipfer, Barbara Strehler, and Astrid Zbinden for their outstanding support in conducting of the study. <h3>Disclosure of Interests</h3> Flavia Zingg Grant/research support from: Gebauer Stiftung, Andrea Gloor: None declared, Christos Polysopoulos Employee of: Previous employment by Roche and IQVIA., Peter Villiger Speakers bureau: Roche, MSD, Abbvie, Pfizer, Novartis, Grünenthal, Celgene, Sanofi, Chugai, Consultant of: Roche, MSD, Abbvie, Pfizer, Novartis, Celgene, Sanofi, Bristol-Meyers-Squibb(BMS), Grant/research support from: Roche, MSD, Abbvie, Britta Maurer Speakers bureau: Boehringer-Ingelheim, GSK, Novartis as well as congress support from Medtalk, Pfizer, Roche, Actelion, Mepha, and MSD, Consultant of: Novartis, Boehringer Ingelheim, Janssen-Cilag, GSK, Grant/research support from: AbbVie, Protagen, Novartis Biomedical, Lisa Christ Shareholder of: Gilead Sciences and F. Hoffmann-La Roche Ltd, Consultant of: Bristol-Myers Squibb and Novartis, Grant/research support from: Gilead Sciences, F. Hoffmann-La Roche Ltd, and Pfizer.